B lineage-restricted rearrangement of a human Ig kappa transgene

Eur J Immunol. 1997 Jul;27(7):1626-31.

Abstract

To study the control of immunoglobulin kappa light chain gene rearrangement, we generated transgenic mice carrying a germ-line human kappa minilocus (HK) containing the J kappa-proximal V gene, V kappa IV, the V-J intergenic region, the five J kappa segments and the C kappa gene. This construct includes the intronic, but not the 3' kappa enhancer. Rearrangement of the HK transgene was found to be lymphoid specific and restricted to the B cell lineage. Quantification of kappa gene rearrangement in pre-B cell lines established from HK transgenic mice showed that, like endogenous kappa genes, rearrangement of the transgene is repressed in mu-negative early B cell precursors. These results indicate that rearrangement of the HK transgene is subjected to the same B/T cell and developmental regulation as V kappa-J kappa rearrangement at the endogenous locus. Comparison with an unrearranged kappa transgenic construct lacking the V-J intergenic region, suggests that this region, or elements associated with the proximal V gene, may act to restrict kappa gene rearrangement to the B cell lineage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism*
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell Line
  • Gene Expression / immunology
  • Gene Rearrangement, B-Lymphocyte / immunology*
  • Genes, Immunoglobulin / immunology*
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Hybridomas
  • Immunoglobulin Joining Region / chemistry
  • Immunoglobulin Joining Region / genetics
  • Immunoglobulin Variable Region / chemistry
  • Immunoglobulin Variable Region / genetics
  • Immunoglobulin kappa-Chains / chemistry
  • Immunoglobulin kappa-Chains / genetics*
  • Mice
  • Mice, Transgenic
  • Recombination, Genetic / immunology
  • Transgenes / immunology*

Substances

  • Immunoglobulin Joining Region
  • Immunoglobulin Variable Region
  • Immunoglobulin kappa-Chains